5-159971902-C-T

Variant names:

• chr5-159971902-C-T
• rs1195785055
• NM_000679.4:c.973C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000679.4(ADRA1B):​c.973C>T​(p.Pro325Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000001 in 999,552 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P325T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: ADRA1B NM_000679.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81
• Publications: 0 publications found

Genes affected

ADRA1B (HGNC:278): (adrenoceptor alpha 1B) Alpha-1-adrenergic receptors (alpha-1-ARs) are members of the G protein-coupled receptor superfamily. They activate mitogenic responses and regulate growth and proliferation of many cells. There are 3 alpha-1-AR subtypes: alpha-1A, -1B and -1D, all of which signal through the Gq/11 family of G-proteins and different subtypes show different patterns of activation. This gene encodes alpha-1B-adrenergic receptor, which induces neoplastic transformation when transfected into NIH 3T3 fibroblasts and other cell lines. Thus, this normal cellular gene is identified as a protooncogene. This gene comprises 2 exons and a single large intron of at least 20 kb that interrupts the coding region. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000679.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1B	NM_000679.4	MANE Select	c.973C>T	p.Pro325Ser	missense	Exon 2 of 2	NP_000670.1	P35368

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1B	ENST00000306675.5	TSL:1 MANE Select	c.973C>T	p.Pro325Ser	missense	Exon 2 of 2	ENSP00000306662.3	P35368
	ADRA1B	ENST00000865014.1		c.973C>T	p.Pro325Ser	missense	Exon 5 of 5	ENSP00000535073.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00000668 AC: 1 AN: 149794 AF XY: 0.0000118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000100 AC: 1 AN: 999552 Hom.: 0 Cov.: 40 AF XY: 0.00000207 AC XY: 1 AN XY: 483416

African (AFR) AF: 0.00 AC: 0 AN: 20096

American (AMR) AF: 0.00 AC: 0 AN: 14664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11426

East Asian (EAS) AF: 0.00 AC: 0 AN: 13374

South Asian (SAS) AF: 0.0000285 AC: 1 AN: 35124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3776

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840878

Other (OTH) AF: 0.00 AC: 0 AN: 35244

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D
Eigen	Benign	-0.024
Eigen_PC	Benign	0.010
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.8
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.19
Sift	Benign	0.038	D
Sift4G	Benign	0.16	T
Polyphen		0.37	B
Vest4		0.48
MutPred		0.51		Loss of catalytic residue at P325 (P = 0.0063)
MVP		0.81
MPC		1.1
ClinPred		0.96	D
GERP RS		1.5
Varity_R		0.46
gMVP		0.67
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1195785055; hg19: chr5-159398909;